Liver cells isolated and established in culture after in vivo administration of diethylnitrosamine to rats were found to contain a characteristic cytoplasmic lesion which was heritably maintained in progeny populations. We plan to investigate the nature of this carcinogen-induced abnormality which resembles the Mallory body seen in patients with certain types of liver cirrhosis, and to determine the relationship of specific cytoskeletal changes to oncogenesis. We will employ electron microscopic analyses, polyacrylamide gel electrophoresis and two-dimensional gel-electrophoresis-autoradiography of cell extracts to characterize the cytoplasmic abnormality. We will use cell-cell hybridization techniques to determine whether the carcinogen-induced changes are due to a mutation.